This proposal is part of an effort and long range international collaboration to develop research projects in genetic epidemiology and anthropology of mental illnesses in a primary health care setting in the Central Andean region populated by Kolla people, spanning the north of Argentina, Bolivia and Peru. The Kolla people of this region, known by the ancient name of Tawantisuyu, is homogeneous culturally and ethnically in spite of varying degrees of bilinguality of Quechua (their native language) with Spanish. We began this effort in the north of Argentina, training local community members acting as primary health agents in the detection and recognition of severe mental illness, as well as the training of mental health professionals familiar with Kolla culture and language in the use of standardized diagnostic and cognitive assessment instruments that have been validated in transcultural studies. This R21 proposal focuses on capacity building, training of local mental health personnel on the use of standardized diagnosis and neuropsychological assessment, and translation to the native language and validation of the instruments for this purpose. As part of the validation process we propose to carry out a pilot evaluation of subjects with schizophrenia, their first degree relatives, and matched population controls, following the model of an ongoing, independently funded, genetic study of an endophenotype in neuroleptic naive persons with schizophrenia. Parkinsonism is highly prevalent in neuroleptic-naive patients with schizophrenia, and its presence is associated with greater susceptibility to neuroleptic-induced side effects, lack of treatment compliance, and poorer outcome. Also, parkinsonism may be closely related with the deficit syndrome associated with an endophenotype of schizophrenia, and negatively associated with smoking. We have identified a population of patients with schizophrenia that, due to geographical and language difficulties, are largely naive to antipsychotic drug treatment throughout the course of illness. Ongoing data collection in the province of Jujuy, Argentina, aims to study the clinical characteristics, cognitive performance, smoking habits, imaging findings, and genetics of the movement disorder in these patients, their first degree relatives, and culturally appropriate controls. Now we propose to translate, adapt and validate the assessment tools in Quechua language in order to expand the sample to full multiplex pedigrees in the same ethnic group in Argentina, Peru and Bolivia. Additionally, we propose to pilot data collection on multiplex families with the long term goal of carrying out family-based association genetic studies as part of future grant applications. PUBLIC HEALTH RELEVANCE: The potential impact of this project cannot be overemphasized, in that 1) it will provide essential training for bilingual clinicians in the use and validation of standardized neuropsychiatry assessment tools, culturally adapted to the Kolla population in their own language, thus eliminating an enormous barrier to access to mental health care for these communities; 2) it will help build a system of access to mental health care by Quechua speaking persons (the most numerous language minority in the Americas), by creating a working network of Quechua-speaking mental health professionals which currently does not exist; 3) availability of empirically based, phenomenological descriptions of mental symptoms will provide a unique tool for studies focusing on traditional medicine conceptions of mental illness; and lastly, the major relevance of the proposed research lies on the possibility of testis if a neurobiologically well defined set of individual characteristics is genetically determined. Because these deficits possibly predate the onset of psychosis, we believe our strategy might provide tools for early detection and early intervention, possibly leading to prevention of psychosis in subjects at-risk for schizophrenia. We anticipate that our research strategy may indicate new ways to study and address the increased vulnerability of schizophrenic patients to nicotine dependence.